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基于网络药理学的余甘子保健作用机制研究
何志贵1, 杜密英1, 徐祥林,等1
桂林旅游学院 休闲与健康学院
摘要:
【目的】探索余甘子(Phyllanthus emblica L.)具食疗保健作用的有效成分和保健作用机制,为余甘子的开发利用提供参考。【方法】首先分别以“余甘子”、“Phyllanthus emblica”或我国台湾和香港地区的余甘子拉丁名“Phyllanthi fructus”为关键词,在中药化学数据库、传统中药化学成分及靶标数据库和台湾传统中药化学成分数据库中对其化学成分进行检索;在此基础上,筛选出口服利用度≥20%的有效成分,进而通过STRING数据库、BioGRID数据库、STITCH数据库和CTD数据库对有效成分的蛋白靶标进行筛选,最后通过靶标的基因本体论(gene ontology,GO)、KEGG(kyoto encyclopedia of genes and genomes)代谢通路和疾病本体论(disease ontology,DO)的富集分析,阐明余甘子保健功效成分的潜在作用机制。【结果】对余甘子化学成分初步的检索与核定发现,其含有亚油酸、并没食子酸、没食子酸、诃子次酸、诃子酸等10种具不同结构的化合物;经口服利用度筛选后,确定油酸、没食子酸、并没食子酸和诃子酸是余甘子中具潜在保健功效的有效成分;进一步的药物 靶标互作分析发现,这些功效成分可作用于前列腺素G/H合酶、维甲酸类受体、内源激素类受体和谷胱甘肽硫转移酶。GO富集分析结果表明,在生物学过程中,余甘子有效成分的靶标在甾体类激素响应、谷胱甘肽及其衍生物的生物合成和代谢过程等条目下富集;分子功能中,余甘子有效成分的靶标在氧化还原酶活性、过氧化物酶活性和谷胱甘肽转移酶活性等条目下显著富集。基于KEGG代谢通路的富集分析结果显示,余甘子功效成分靶标与多重肿瘤生物学途径及动脉粥样硬化、抗病毒、乙型肝炎和丙性肝炎等通路相关。DO的富集分析结果显示,余甘子活性成分靶点与前列腺癌、腺体癌、头颈部肿瘤、神经胶质瘤等恶性肿瘤存在重要联系。【结论】余甘子的功效成分可以通过谷胱甘肽硫转移酶、前列腺素G/H合酶等途径发挥抗肿瘤耐药性和抗动脉粥样硬化等功效,是研发具有抗炎、抗衰老、降血脂和免疫调节疗效保健食品的重要植物资源。
关键词:  余甘子  保健功效  网络药理学  谷胱甘肽  前列腺素
DOI:
分类号:
基金项目:广西壮族自治区财政科技计划项目“广西康养特色茶制品关键技术开发与应用”(2018AB49021);广西高校中青年教师基础能力提升项目“不同聚合度三叶青原花青素的体外抗氧化活性分析”(2020KY22007)
Healthy and diet protection mechanism of Phyllanthus emblica (Euphorbiaceae) based on network pharmacology
HE Zhigui,DU Miying,XU Xianglin,et al
Abstract:
【Objective】To provide information for development and use of Phyllanthus emblica L.,the effective chemicals and working mechanism were investigated.【Method】Using P. emblica and its Taiwanese synonym P. fructus as retrieval words,the chemical constituents of P. emblica collected by TCM database (traditional Chinese medicine),TCMSP (chemical constituents and its targets of traditional Chinese medicine) database,and TCM@TAIWAN database (chemical constituents of traditional Chinese medicine in Taiwan) were searched and verified.Then,the oral availability (≥20%) was selected as the basic threshold for screening and filtering standard for active ingredients,and protein targets of active ingredients were screened by STRING database,BioGRID database,STITCH database and CTD database.Finally,the enrichment analysis on those active ingredients was conducted with GO,KEGG and DO database.【Result】With the results derived from TCM,TCMSP and TCM@TAIWAN database,ten chemicals with different chemical structures were retrieved and verified,including linoleic acid,ellagic acid,gallic acid,chebulic acid,chebulinic acid,chebulagic acid and terchebin.Further screening with the threshold of oral availability (≥20%) identified four chemicals of linoleic acid,ellagic acid,gallic acid and chebulic acid as potentially efficacy chemicals.Subsequently,the chemical-target interaction analysis revealed that these active components may play regulating effect through prostaglandin G/H synthase (PTGS1 and PTGS2),retinoic acid receptor (RXRA and RXRG),endogenous hormone receptor (ESR1,AR and PR) and glutathione sulfur transferase (GSTA1,GSTA2,GSTM1,GSTM2 and GSTP1).Finally,the enrichment analysis showed that these proteins were enriched in glutathione metabolism,steroid metabolism,toxic response of foreign substances and metabolic process with high gene overlap in hepatocellular carcinoma,small cell lung cancer,prostate cancer,platinum resistance and atherosclerosis.【Conclusion】These results suggested P. emblicais active chemicals had anti-arteriosclerosis and drug resistance reduction functions through glutathione sulfur transferase or prostaglandin synthase pathway.It is also an important local plant resource for developing healthy food with anti-inflammatory,anti-aging,lipid lowering and immune regulation effects.
Key words:  Phyllanthus emblica L.  healthy and diet protection efficacy  network pharmacology  glutathione sulfur transferase  prostaglandin